Clustering with dendritic cells precedes and is essential for T-cell proliferation in a mitogenesis model

Several antigen-specific immune responses are known to occur in discrete aggregates of dendritic cells (DC) and lymphocytes. We have used a polyclonal model, the mitogenesis of T cells that have been modified with sodium periodate, to evaluate the significance of cell-cell clustering. Firstly, we found that clustering precedes the onset of DNA synthesis by a day. Within 2 hr, virtually all of the added dendritic cells and most of the T cells that will respond have formed clusters. The T cells then progressively release and become responsive to interleukin-2 over 18 hr and DNA synthesis begins at 24 hr. Secondly, clustering with dendritic cells appears to be essential for mitogenesis. If dendritic cells are eliminated, the clusters disassemble and subsequent proliferation is reduced. Clustering and proliferation can be restored with dendritic cells that are syngeneic or allogeneic with the initial inoculum. DC are inactive if they are treated with ultraviolet light, formaldehyde or heat. Thirdly, the non-clustered cells do not synthesize DNA even when mixed with the clusters. However, non-clusters will respond when supplemented with additional DC. We conclude that clustering with DC precedes and seems essential for T-cell mitogenesis in the periodate model.